Most Appropriate Next Step: Complete Blood Count (CBC)
The most appropriate next step is to obtain a CBC with differential (Option A), as the family history of leukemia and retinoblastoma raises concern for Li-Fraumeni syndrome or another hereditary cancer predisposition syndrome, and a CBC is the foundational screening test to identify cytopenias, abnormal white blood cell counts, or circulating blasts that may suggest leukemia. 1
Clinical Reasoning
Why CBC is the Priority
- A manual differential is critical because automated counters may miss abnormal cells, and manual review is essential for identifying blasts or dysplastic features that could indicate leukemia 1
- The combination of family history (leukemia + retinoblastoma) is highly suggestive of Li-Fraumeni syndrome (TP53 mutation), which predisposes to multiple cancers including leukemia, brain tumors, soft tissue sarcomas, and retinoblastoma 2
- The recent URTI does not exclude malignancy—many pediatric leukemias present following viral illnesses, and attributing findings to recent viral infection without excluding malignancy first is a critical pitfall to avoid 1
What Happens if CBC is Abnormal
If the CBC reveals concerning findings (cytopenias, elevated white count, or abnormal cells), the following urgent workup should be initiated:
- Lactate dehydrogenase (LDH) and uric acid to assess tumor burden and tumor lysis syndrome risk 1
- Comprehensive metabolic panel to evaluate renal and hepatic function 1
- Peripheral blood flow cytometry to characterize lymphocyte subsets and identify abnormal blast populations 1
- Urgent hematology/oncology referral for bone marrow aspiration and biopsy with cytogenetics, immunophenotyping, and molecular studies 1
Why Other Options Are Not First-Line
- CXR (Option B): Not indicated as initial screening in an asymptomatic child with resolved URTI; would only be relevant if respiratory symptoms persisted or CBC suggested leukemia with mediastinal involvement 3
- Ophthalmology referral (Option C): While important given family history of retinoblastoma, this does not address the immediate concern for leukemia in the patient; ophthalmologic screening would be part of comprehensive Li-Fraumeni surveillance but is not the urgent first step 2
- BRCA 1&2 testing (Option D): BRCA mutations are associated with breast and ovarian cancer, not with the leukemia-retinoblastoma pattern seen here; TP53 mutation testing would be the appropriate genetic test if Li-Fraumeni syndrome is suspected, but CBC must come first 2
Genetic Counseling Considerations
- Genetic counseling and TP53 mutation testing should be considered if CBC reveals cytopenias or abnormal cells, or even if CBC is normal given the striking family history pattern 1, 2
- The triad of brain tumor, leukemia, and retinoblastoma in a family is pathognomonic for Li-Fraumeni syndrome 2
- If TP53 mutation is confirmed, the child will require intensive lifelong cancer surveillance including annual whole-body MRI, brain MRI, and other age-appropriate screening starting immediately 2
Common Pitfalls to Avoid
- Never delay CBC while arranging specialty referrals—this simple test can be obtained immediately and will guide all subsequent management 1
- Never rely solely on automated differential—manual review by an experienced technician or pathologist is mandatory to identify abnormal cells 1
- Never assume the recent URTI explains everything—respiratory viruses are common in children with leukemia, and viral infections can precede or coincide with leukemia diagnosis 4, 5, 6
- Never overlook limited family history as excluding hereditary cancer syndromes—de novo mutations and incomplete penetrance can obscure family patterns 2